The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.

Objective: To study the effect and protection mechanism of sea buckthorn sterol on acute liver injury induced by carbon tetrachloride (CCl4) in rats. Methods: CCl4 was used to make a rat model of acute liver injury. The rats were divided into six groups including blank control group, model control group, bifendate treated positive control group, low-, medium-, and high-doses of sea buckthorn sterol treated groups. The enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), gamma-glutamyl transpeptidase (γ-GT), and catalase (CAT) were investigated. Total antioxidant capacity (T-AOC), total protein (TP), and the content of malondialdehyde (MDA), the level of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in liver tissues were determined. HE staining was used for the observation of inflammatory changes of liver tissues. The endoplasmic reticulum and mitochondria in liver tissues were observed by electron microscope. Wide range of targeted technologies were used for the detection of the full-spectrum metabolome, and metabolome differences among samples were investigated by means of the combination of UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis. Transcriptomics were studied using the RNA-SEQ method. Based on comparison results, gene expression levels were analyzed, and differentially expressed genes were identified according to their expression levels in different samples. Results: After the treatment of sea buckthorn sterol, the activities of SOD, GSH-Px, CAT, T-AOC, and TP in liver tissues were increased, while the activities of γ-GT, COX-2, and PGE2 were decreased, and the content of MDA was also reduced. Sea buckthorn sterol can reduce the inflammatory lesions in liver tissues, and the damage of the structure of endoplasmic reticulum and mitochondria of liver cells were significantly alleviated compared with the model group. The levels of L-malic acid, 7Z, 10Z, 13Z, 16Z, 19Z-docosapentaenoic acid, creatine, N-acetyl-l-alanine, N-acetyl-aspartic acid, trigonelline, 4-guanidine butyric acid, N-amidine L-aspartic acid, CE(16:1), CE(18:2), PE(16:1/16:0), DG(16:0/18:02/0:0), TG(14:0/18:0/20:4), TG(16:0/18:0/20:4), TG(16:0/16:1/22:5), N-glycine-l-leucine, and FFA(6:0) were significantly restored after the treatment of sea buckthorn sterol. Sea buckthorn sterol could participate in the citric acid cycle, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, niacin and niacinamide metabolism, fat digestion and absorption, and glycerophospholipid metabolism. Besides, the expressions of Cyp1a1, Noct, and Tubb6 could be regulated by sea buckthorn sterol, and thus the metabolic damage by CCl4 was reduced. Conclusion: Sea buckthorn sterol could improve liver function in the animal model of CCl4-induced acute liver injury in rats. The mechanism of liver protection is likely related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of inflammatory response.